The Viral Epidemiology Branch (VEB) has used a variety of approaches to define the nature and magnitude of malignancies associated with HIV-1 and other chronic infections, including analyses of population-based data, prospective cohort studies, and laboratory investigations. We are currently initiating a limited follow-up of 2,480 subjects with CDC-defined AIDS (i.e., <200 CD4+ T-cells/?l) recruited in 1998-99. Nested case-control studies of incident cancers are planned, utilizing the detailed clinical and interview data and banked blood specimens (plasma and cryopreserved PBMC) collected at enrollment. Our two previous cohort studies of HIV-infected hemophilia patients have been incorporated into a larger cohort which includes HIV uninfecteds, whose prospective followup for cancer is just being initiated. These cohorts will be applied to studies of potential risk factors for AIDS-related malignancy, including genetic polymorphisms and/or altered baseline levels of cytokines and other immune factors, chromosomal translocations, EBV and HHV-8 viral loads, antibody titers, and cell mediated immunity, and environmental exposures and medications. We are continuing our studies of EBV infection and immune response as a causative factor in pediatric AIDS-related cancer, and have initiated collaborations to extend this work to AIDS-related lymphomas in adults. We are also collaborating with the NIDDK to study HHV-8 reactivation in HIV-positive renal allotransplant recipients. In collaboration with the Occupational Epidemiology Branch, we are continuing our investigations of cytokine polymorphisms as risk factors for gastric cancer. In a collaboration with the Veterans' Administration, we are extending our previous mortality followup of hepatitis C seropositive Air Force recruits from the 1950s, with physical examinations and medical record reviews of surviving cohort members. We are also initiating laboratory studies of another HCV-infected VA cohort which dates from the 1970s, for which we will assess viral load and genotype as predictors of subsequent liver disease.